Objective: To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts.Methods: Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity.
Results:We found focal cortical thinning specifically in areas connected to acute infarcts (p , 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (r 5 20.39, p 5 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter.Conclusions: These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke. Remote cortical effects of acute infarcts critically contribute to functional reorganization after stroke and influence clinical outcome.1,2 We recently identified focal cortical thinning as a potential structural correlate of remote effects after ischemic lesions. In a small retrospective study on 9 patients with inherited small vessel disease, we showed that incident subcortical lacunes are associated with focal thinning in cortex connected to the infarct. 3,4 We attributed these findings to secondary cortical neurodegeneration following damage to the connecting subcortical fiber tracts. However, the study protocol and small sample size precluded a detailed assessment of these tracts and how changes in these tracts relate to changes in the connected cortex. Also, the results were obtained in a rare hereditary condition and were limited to a single infarct mechanism and to chronic, cavitating infarcts.In the current prospective, longitudinal study, we investigated the processes driving secondary neurodegeneration after acute infarcts. We measured changes of cortical thickness and microstructural integrity of connecting white matter tracts over a 6-month interval starting from stroke onset. We tested the following hypotheses: (1) cortical thinning in connected cortical regions is detectable within a few months after an acute infarct; (2) cortical thinning relates to *These authors contributed equally to this work.